NAT10 is upregulated in hepatocellular carcinoma and enhances mutant p53 activity

BMC Cancer

Research Article

Chunfeng Zhang¹  Xiaojuan Du¹  Xiaofeng Liu¹  Qijiong Li²  Min Lu³  Baocai Xing⁴  Kemin Jin⁴ 

[1] Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, 100191, Beijing, China;Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, 510060, Guangzhou, Guangdong, China;Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 100191, Beijing, China;Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, 52 Fucheng Road, 100142, Haidian District, Beijing, China;

关键词: NAT10;    Hepatocellular carcinoma;    Prognosis;    Mutant p53;    Stability;   

DOI  :  10.1186/s12885-017-3570-4

 received in 2016-10-14, accepted in 2017-08-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundN-acetyltransferase 10 (NAT10) is a histone acetyltransferase which is involved in a wide range of cellular processes. Recent evidences indicate that NAT10 is involved in the development of human cancers. Previous study showed that NAT10 acetylates the tumor suppressor p53 and regulates p53 activation. As Tp53 gene is frequently mutated in hepatocellular carcinoma (HCC) and associates with the occurrence and development of HCC, the relationship between NAT10 and HCC was investigated in this study.MethodsImmunohistochemistry (IHC) and western blot analysis were performed to evaluate the NAT10 expression in HCC. Immunoprecipitation experiments were performed to verify the interaction of NAT10 with mutant p53 and Mdm2. RNA interference and Western blot were applied to determine the effect of NAT10 on mutant p53. Cell growth curve was used to examine the effect of NAT10 on HCC cell proliferation.ResultsNAT10 was upregulated in HCC and increased NAT10 expression was correlated with poor overall survival of the patients. NAT10 protein levels were significantly correlated with p53 levels in human HCC tissues. Furthermore, NAT10 increased mutant p53 levels by counteracting Mdm2 action in HCC cells and promoted proliferation in cells carrying p53 mutation.ConclusionIncreased NAT10 expression levels are associated with shortened patient survival and correlated with mutant p53 levels. NAT10 upregulates mutant p53 level and might enhance its tumorigenic activity. Hence, we propose that NAT10 is a potential prognostic and therapeutic candidate for p53-mutated HCC.

【 授权许可】

CC BY   
© The Author(s). 2017